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Dilution Errors: Massive accidental overdoses of BREVIBLOC injection have resulted from dilution errors. Use of BREVIBLOC PREMIXED Injection and BREVIBLOC PREMIXED Double Strength Injection may reduce the potential for dilution errors. Some of these overdoses have been fatal while others resulted in permanent disability. Bolus doses in the range of 625 mg to 2.5 g (12.5-50 mg/kg) have been fatal. Patients have recovered completely from overdoses as high as 1.75 g given over one minute or doses of 7.5 g given over one hour for cardiovascular surgery. The patients who survived appear to be those whose circulation could be supported until the effects of BREVIBLOC injection resolved.
Signs and Symptoms of Overdose: Overdoses of BREVIBLOC (Esmolol Hydrochloride) injection can cause cardiac and central nervous system effects. These effects may precipitate severe signs, symptoms, sequelae, and complications (for example, severe cardiac and respiratory failure, including shock and coma), and may be fatal. Continuous monitoring of the patient is required.
Cardiac effects include bradycardia, atrioventricular block (1st-, 2nd-, 3rd degree), junctional rhythms, intraventricular conduction delays, decreased cardiac contractility, hypotension, cardiac failure (including cardiogenic shock), cardiac arrest/asystole, and pulseless electrical activity.
Central nervous system effects include respiratory depression, seizures, sleep and mood disturbances, fatigue, lethargy, and coma.
In addition, bronchospasm, mesenteric ischemia, peripheral cyanosis, hyperkalemia, and hypoglycemia (especially in children) may occur.
Treatment Recommendations: Because of its approximately 9-minute elimination half-life, the first step in the management of toxicity should be to discontinue the BREVIBLOC infusion. Then, based on the observed clinical effects, consider the following general measures.
Bradycardia: Consider intravenous administration of atropine or another anticholinergic drug or cardiac pacing.
Cardiac Failure: Consider intravenous administration of a diuretic or digitalis glycoside. In shock resulting from inadequate cardiac contractility, consider intravenous administration of dopamine, dobutamine, isoproterenol, or inamrinone. Glucagon has been reported to be useful.
Symptomatic hypotension: Consider intravenous administration of fluids or vasopressor agents such as dopamine or norepinephrine.
Bronchospasm: Consider intravenous administration of a beta2 stimulating agent or a theophylline derivative.
